This invention relates to a long acting diclofenac sodium preparation, and more particularly, to a long acting diclofenac sodium preparation in which a rapidly soluble component is combined with an enteric component having an enteric coating to provide prolonged action.
Diclofenac sodium or sodium 2-(2,6-dichloroanilino)-phenylacetate belonging to a class of non-steroid drugs has as high antiinflammatory, analgesic and antipyretic actions as indomethacin. Highly evaluated for its effectiveness, diclofenac sodium has been widely used clinically in the form of tablets and suppositories.
It is generally known that diclofenac sodium migrates into blood within 30 minutes and reaches the maximum concentration in blood within 2 hours after oral administration and the blood concentration half life is as short as 1.3 hours. Since diclofenac sodium is quickly absorbed in and excreted from blood, it is difficult to maintain in blood for a long time. For this reason, currently commercially available diclofenac sodium tablets must be taken three times a day. In addition, it has been reported that oral administration of diclofenac sodium would often induce various side effects including gastroenteritis. Therefore, there is a strong need for a long acting preparation which can sustain the action of diclofenac sodium in safe over an extended period of time.
Japanese Patent Application Kokai No. 61-44811 (laid open Mar. 4, 1986) proposes a sustained release diclofenac sodium preparation comprising rapid action diclofenac sodium combined with delayed action diclofenac sodium so that the action of diclofenac sodium can be sustained as long as possible. The delayed action component is disclosed as comprising diclofenac sodium covered with a coating of an enteric material or water-insoluble material. The enteric material used is a methacrylic acid-methyl methacrylate copolymer (including methacrylic acid copolymers S and L) which is soluble in water at an acidity level in the range of about pH 6-7. More particularly, the sustained release diclofenac sodium preparation is disclosed as comprising the rapid action component which is made by granulating diclofenac sodium with suitable excipient and binder into granules, and the delayed action component which is made by granulating diclofenac sodium with suitable excipient into granules, and coating the granules with an enteric material predominantly comprising a methacrylic acid-methyl methacrylate copolymer.
It was found that this sustained release diclofenac sodium preparation, especially comprising a delayed action component having an enteric coating of a methacrylic acidmethyl methacrylate copolymer can maintain diclofenac sodium in blood for an extended period of time as compared with conventional commercially available diclofenac sodium preparations. Making further research for the more efficient mass scale production of sustained release diclofenac sodium preparation, we found the following problems.
When the timed release diclofenac sodium preparation is produced in a mass scale, problems arise in the step of coating active component particles with an enteric material. The enteric coating tends to crack in the coating and subsequent drying steps. Coated particles tend to agglomerate and there is a chance for the coating to delaminate or chip away after agglomeration. Coated particles having a particle size in the desired range can be produced only in a limited yield. Once the enteric coating is cracked, chipped or peeled, the enteric component cannot exert its own function of retarding action because the diclofenac sodium of the enteric component will dissolve out before the coated particles reach the intestine. These defective particles fail to achieve the effect of sustaining the action of diclofenac sodium for a prolonged time. Thus, the sustained release diclofenac sodium preparation of the above-cited application is not suitable as such for mass production.